Summary for Overview The proposed Center will perform mechanistic studies of allergen-specific T cell responses in peanut allergic subjects through two synergistic projects. The first project will investigate the phenotypic and functional characteristics of allergen specific T cells in subjects with peanut allergy and subjects that are tolerant to peanut. The second project will investigate changes in the frequency, phenotype, and function of allergen- specific T cells that are associated with immunotherapy. This project will utilize longitudinal clinical samples from a peanut oral immunotherapy trial and samples from a peanut peptide immunotherapy in which subjects will receive intradermal injection of the peanut peptide vaccine. Both projects will utilize cutting edge technologies including metal tag class II tetramer reagents with CyTOF and single cell RNA-seq to study peanut allergen specific T cells. The infrastructure of our Center includes two cores. Core A, the Administrative Core, will oversee scientific progress of the two projects, facilitate data integration between the projects, and provide managerial responsibility and fiscal management for the Center. Core B, the Gene Expression and Systems Immunology Core will be responsible for data analysis for RNA-seq, Flow Cytometry and Mass Cytometry, and will also work with Core A in data management. Benaroya Research Institute has state-of-the- art facilities and technical equipment, established infrastructure for technical support and subject recruitment, and collegial environments to support the research as propose.